By using a compound derived from a Himalayan fungus and used for centuries in Chinese medicine as a jumping off point, scientists have developed a new chemotherapy drug with powerful anti-cancer effects. Doing so involved chemically altering the compound to better infiltrate cancerous cells, which proved to boost its potency by up to 40 times.
The research carried out by University of Oxford scientists in collaboration with biopharmaceutical company Nucana began with a compound called Cordycepin. This naturally-occurring nucleoside analogue has been used to treat inflammatory disease and cancer for hundreds of years, but runs into several barriers that severely limit its effectiveness when deployed to tackle tumors.
This is largely because as Cordycepin enters the bloodstream, it is rapidly broken down by an enzyme called ADA. What is left then needs to be carried into cancer cells by a nucleoside transporter, and then converted into an anti-cancer metabolite called 3’-dATP. This is a lot of hoops for the humble, naturally-occurring Cordycepin to jump through and means only meager amounts wind up making it into the tumor.
Nucana looked to harness the anti-cancer potential of Cordycepin and better equip it to navigate these considerable roadblocks, through what it calls ProTide technology. This is designed specifically to address the shortcomings of nucleoside analogues. It works by attaching small chemical groups to the compound that make it more resistant to breakdown in the bloodstream, and also enables them to enter cancer cells without the help of nucleoside transporters. The upshot is far greater levels of anti-cancer metabolites are generated and activated inside tumor cells.
This enhanced form of Cordycepin is dubbed NUC-7738, and the novel chemotherapy drug was assessed through in vitro studies, demonstrating that it overcomes the resistance mechanisms that inhibit its parent compound. Tumor samples obtained from ongoing Phase I clinical trials were then used to probe its effectiveness in humans, with these experiments validating the earlier findings.
Altogether, the authors conclude NUC-7738 to have as much as 40 times the potency of the naturally-occurring Cordycepin, and has limited toxic side effects. The scientists are now continuing to assess its performance in the Phase 1 clinical trial on patients with advanced solid tumors, and are planning to follow that up with Phase 2 trials to further evaluate its clinical potential.
The research was published in the journal Clinical Cancer Research.
Source: University of Oxford
